Our application of emerging tools in cryo-EM to the study of membrane proteins and their conformational changes continues to grow. Progress on two projects is summarized below. G protein-coupled receptors (GPCRs) comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways through coupling with downstream signaling mediators, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestins. The structural mechanisms that define how GPCRs selectively couple to a specific type of G protein or arrestin remain unknown. Using cryo-EM, we have now shown in a paper published in the journal Nature in June 2018, that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi alpha-subunit, which is wedged into the cytoplasmic face of the transmembrane helix bundle and directly contacts the N-terminus of Helix-8 of rhodopsin. Comparison of the structures of inactive, Gi- and arrestin- bound forms of rhodopsin with inactive and Gs- bound forms of the beta-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with Gs, Gi, and arrestin recognition by activated GPCRs. Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv channels appear to have captured an open state even though a non-conducting C-type inactivated state would predominate in membranes in the absence of a transmembrane voltage. However, structures for a voltage-activated ion channel in a lipid bilayer environment have not yet been reported. In a paper published in August 2018 in the journal eLife, we report the structure of the Kv1.2-2.1 paddle chimera channel reconstituted into lipid nanodiscs using single-particle cryo-electron microscopy (cryo-EM). At a resolution of 3 Angstrom for the cytosolic domain and 4 Angstrom for the transmembrane domain, the structure determined in nanodiscs using cryo-EM is remarkably similar to the previously determined X-ray structure. Our findings show that large differences in structure between detergent and lipid bilayer environments are unlikely, and enable us to propose possible structural mechanisms for C-type inactivation.